Plasma retinol, carotene and vitamin E concentrations and lung function in a crocidolite-exposed cohort from Wittenoom, Western Australia: a cohort study

Published
2005-05-11

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Authors

Helman S Alfonso, School of Population Health, University of Western Australia, Perth, Western Australia, Australia, School of Public Health, Curtin University of Technology, Perth, Western Australia

Lin Fritschi, School of Population Health, University of Western Australia, Perth, Western Australia, Australia

Nicholas H de Klerk, School of Population Health, University of Western Australia, Perth, Western Australia, Australia, Department of Biostatistics and Genetic Epidemiology, Telethon Institute for Child Health Research, Perth, Western Australia, Australia

Gina Ambrosini, School of Population Health, University of Western Australia, Perth, Western Australia, Australia

Nola Olsen, School of Population Health, University of Western Australia, Perth, Western Australia, Australia

A William Musk, School of Population Health, University of Western Australia, Perth, Western Australia, Australia, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia

Statistical Analysis

To assess the relationships between lung function and plasma vitamin concentrations, the dependentvariables (FEV1 and FVC) were regressed on time, controlling for demographic characteristics (sex, age and height), asbestos exposure and tobacco smoking. Plasma levels of retinol, carotene and vitamin E (as quartiles) were included in the model, both separately and at the same time. A lineartrend was also evaluated by including the raw values (continuos variable) of each plasma vitamin concentration. The main effect of each vitamin concentration was interpreted as the level of lung function at entry into the study, while the interaction of each vitamin concentration with time of follow up (in years) was interpreted as the annual change of lung function over time [18]. Specifically, levels of lung function at entry into the Program correspond to the values of lung function (or differences between groups) when time of follow up was zero. The analyses were performed initially for each vitamin separately, and then by including simultaneously the three vitamin values into the model.

Results

A total of 5,750 determinations from 1,378 subjects who had at least one test of both spirometry and plasma vitamin concentrations were analysed. The demographic characteristics and exposure histories at the first visit showed that former workers had lower levels of FEV1 and FVC than ex-residents (Table1). Workers were morelikely to be male and residents were female. Workers were exposed to higher cumulative amounts of asbestos (median 6.40 fibres/ml per year, interquartile range 1.92–26.01), and included a higher proportion of participants with radiographic asbestosis. Although ex-residents were exposed to asbestos for longerperiods of time, their cumulative asbestos exposure was lower, as the intensity of exposure was much higher in the mining and milling processes. Ex-residents tended to be exposed to asbestos at a younger age than workers. In addition, workers included a higher proportion of ever-smokers. Initial levels of plasma vitamins were similar between workers and ex-residents. At the first visit, plasma retinol concentrations were not significantly correlated with plasma carotene concentrations (r = -0.006, p = 0.84); plasma concentrations of retinol and vitamin E were highly correlated (r = 0.33, p = <0.0001); and carotene and vitamin E concentrations tended to be correlated (r = 0.047, p = 0.08).

Table 1

Residents

Workers

Participants, n (%)

567 (41.1)

811 (58.9)

Male, n (%)

270 (47.6)

749 (92.4)

FEV1, litres a

2.9 (0.9)

2.7 (0.7)

FVC, litres a

3.7 (1.1)

3.6 (0.9)

Age, yr a

50.8 (12.5)

59.2 (7.7)

Height at baseline, cm a

168 (9.5)

171 (7.5)

Cumulative asbestos, f/ml-year a

6.9 (7.5)

24.5 (47.8)

Age at first asbestos exposure, yr a

13.9 (12.7)

24.8 (6.1)

Radiographic asbestosis, n (%)

8 (1.4)

143 (17.6)

Current-smokers, n (%)

114 (19.6)

182 (21.8)

Ex-smokers, n (%)

183 (31.5)

452 (54.2)

Never-smokers, n (%)

284 (48.9)

199 (23.9)

Plasma retinol, (μmol/L)a

2.70 (0.70)

2.70 (0.69)

Plasma carotene, (μmol/L)a

1.38 (1.57)

1.38 (1.52)

Plasma vitamin E, (μmol/L)a

38.13 (13.85)

35.43 (11.40)

Demographic characteristics of participants at first visit a

Twenty-fourpercent of participants had one visit at which lung function and plasma vitamins were measured, 21% had two measurements, 17% had three, 14% had four, 10% had five, and 14% had more than 5 measurements during the period of observation. The Vitamin A Program initially gavepreference to enrolling workers, who were mostlymales, because of their greater risks of developing asbestos-related diseases. Therefore they had more spirometric measurements per person and a longer follow-up time (Table 2).

Table 2

Residents

Workers

Total lung function and blood tests, n (%)

1942 (33.7)

3898 (66.2)

Measurements per person, a

3.43 (1.5)

4.7 (2.5)

Follow up, years, a

3.0 (1.7)

5.4 (3.3)

Months between measurements,a

14.0 (4.8)

16.5 (9.7)

Characteristics of the follow up of the study cohort a

After adjusting for confounders, plasma retinol concentrations (as a single vitamin in the model) at entry into the study were not associated with levels of lung function (Table 3), (p-value for linear trend = 0.36 for FEV1, p = 0.50 for FVC). For example, people in the thirdquartile (Q3) have, on average, 4.4 ml more of FEV1 and 6.6 ml more of FVC, compared to those in the first quartile (Q1). However, these differences were not statistically significant as the confidence intervals containnegative values. However, higher concentrations of plasma retinol were associated with a lower rate of decrease in lung function over time: the annual decline in people in the highest quartile of retinol concentration was 11.3 ml (95% CI = 4.8–17.7) of FEV1 and 18.6 ml (95% CI = 10.4–26.8) of FVC less steeper than those in the lowest quartile. The linear trends were significant for FEV1 and FVC (not shown in table 3).

Higher plasma carotene concentrations (as a single vitamin in the model) were associated with higher levels of lung function at entry into the study (Table 4). On the contrary, higher plasma carotene concentrations were associated with a steeper decline of lung function. The annual decline in people in the highest quartile was 9.3 ml (95% CI = 2.6–15.9) of FEV1, and 8.3 ml (95% CI = 0–16.5) of FVC less steeper than those in the lowest quartile (Table 4). Linear trends were significant for both levels and rates of change of lung function (not shown).

Higher plasma vitamin E concentrations (as a single vitamin in the model) were associated with higher levels of lung function at entry into the study (Table 4). However, higher plasma vitamin E concentrations were associated with a steeper decline of lung function. The decline in people in the highest quartile was 7.9 ml (95% CI = 14.3-1.6) per year in FEV1, and 13.9 ml (95% CI = 21.9-6.0) per year in FVC, compared to those in the lowest quartile (Table 4). Linear trends were significant for both levels and rates of change of lung function (not shown).

Including retinol, carotene and vitamin E plasma concentrations in the same model, and adjusting for potential confounders, higher plasma retinol concentrations were associated with higher levels of lung function, as well as a slower decline in the annual rate of change of lung function (Table 6). Plasma carotene concentrations were associated with higher levels of lung function at entry, but with a steeper decline in lung function over time. Plasma vitamin E concentrations were associated with lower levels of lung function at entry into the study, but not associated with changes over time.

Table 6

Plasma vitamin concentrations (μMol/L)

FEV1 (ml) Estimate (SD)

p-value

FVC (ml) Estimate (SD)

p-value

Retinol

Level

13.9 (7.5)

0.06

16.6 (9.5)

0.08

Change

3.5 (1.5)

0.02

5.7 (1.9)

0.00

Carotene

Level

14.6 (3.6)

0.00

13.1 (4.5)

0.00

Change

-2.6 (1.0)

0.01

-3.5 (1.3)

0.01

Vitamin E

Level

-1.0 (0.4)

0.01

-2.0 (0.5)

<0.01

Change

0.07 (0.09)

0.38

0.2 (0.1)

0.13

Relationships between lung function and retinol, carotene and vitamin E concentrations, when the three vitamins were simultaneously included in the model*

The analysis was also performed for alpha- and beta-carotene. As was reported for total carotene concentrations, both alpha- and beta-carotene concentrations were associated with higher levels of lung function, and inversely related to the change of lung function over time (not shown).

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Discussion

After adjusting for potential confounders and the joint effect of the plasma vitamin levels, plasma retinol concentrations were associated with higher levels of lung function as well as a slower rate of decline over time; plasma carotene concentrations (or alpha and beta-carotene) were associated with higher levels of lung function, but with a steeper decline in lung function; plasma vitamin E concentrations were associated with lower levels of lung function at entry, but not associated with amount change of lung function over time. The observedtendency in the separate analysis for each vitamin (Tables3 to 5) was similar to the results obtained when the three variables were jointly included in the model, except for the effect of plasma retinol concentrations, which becamepositively associated with levels of lung function at the entry in the Vitamin A Program. We have previously shown that mortality in subjects with asbestosis was inversley related to plasma concentrations of retinol and vitamin E (at first visit and during the follow up period), while carotene concentrations at the first visit were associated with lower mortality but not during the follow up period [33]

Due to self-selection into the Vitamin A Program this population may not be representative of the wholecohort exposed to crocidolite at Wittenoom. People who participated in the Program were younger and had higher cumulative asbestos exposure [7]. The results from this study, may not apply to subjects with lower exposure to crocidolite or older age groups.

This longitudinal study demonstrates a beneficial relationship between plasma levels of retinol and level and rate of decline of lung function as measure by FEV1 and FVC, while showing no such beneficial effect for plasma levels of beta-carotene.

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